Delta-9-tetrahydrocannabinol / THC

evidence_span

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experimental_model

Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes

exposure

Cannabinoid concentration-response on adenylate cyclase

limitations

One of the two founding pharmacology papers for Gi coupling. A transformed cell line, and cAMP is a proximal readout.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Cultured neuroblastoma cells

plain_language

The drug turns down the enzyme that makes the cell’s main second messenger.

primary_references

[thc-p6092901] Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. (1984). https://pubmed.ncbi.nlm.nih.gov/6092901/ DOI: 10.1016/s0026-895x(25)15066-9

tissue_or_cell_type

Cell membranes

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 153–164

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes · source_derived_draft · unverified_draft

### thc-cannabinoid-inhibits-ac Cannabinoids inhibited adenylate cyclase in neuroblastoma cell membranes with a pharmacology matching their psychoactivity. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The drug turns down the enzyme that makes the cell’s main second messenger. organism: Cultured neuroblastoma cells tissue_or_cell_type: Cell membranes experimental_model: Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes limitations: One of the two founding pharmacology papers for Gi coupling. A transformed cell line, and cAMP is a proximal readout. exposure: Cannabinoid concentration-response on adenylate cyclase evidence_span: {"source_cache": "artifacts/thc-research/6092901.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5", "start_char": 0, "end_char": 1329, "text_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5"} [thc-p6092901] Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. (1984). https://pubmed.ncbi.nlm.nih.gov/6092901/ DOI: 10.1016/s0026-895x(25)15066-9

evidence_span

{"source_cache": "artifacts/thc-research/9651215.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60", "start_char": 0, "end_char": 974, "text_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60"}

experimental_model

Prolonged THC administration with hippocampal histology

exposure

Chronic high-dose THC exposure

limitations

A structural damage endpoint at high chronic doses in rats. The doses are far above ordinary human exposure, which is the main limit on reading it across.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rat

plain_language

At high chronic doses in rats the same structure shows physical damage.

primary_references

[thc-p9651215] Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. (1998). https://pubmed.ncbi.nlm.nih.gov/9651215/ DOI: 10.1523/jneurosci.18-14-05322.1998

tissue_or_cell_type

Hippocampus

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 478–489

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prolonged THC administration with hippocampal histology · source_derived_draft · unverified_draft

### thc-thc-hippocampal-damage Prolonged THC administration produced hippocampal neurotoxicity in rats. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: At high chronic doses in rats the same structure shows physical damage. organism: Rat tissue_or_cell_type: Hippocampus experimental_model: Prolonged THC administration with hippocampal histology limitations: A structural damage endpoint at high chronic doses in rats. The doses are far above ordinary human exposure, which is the main limit on reading it across. exposure: Chronic high-dose THC exposure evidence_span: {"source_cache": "artifacts/thc-research/9651215.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60", "start_char": 0, "end_char": 974, "text_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60"} [thc-p9651215] Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. (1998). https://pubmed.ncbi.nlm.nih.gov/9651215/ DOI: 10.1523/jneurosci.18-14-05322.1998

evidence_span

{"source_cache": "artifacts/thc-research/21078841.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9", "start_char": 0, "end_char": 1727, "text_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9"}

experimental_model

Controlled oral THC and oromucosal cannabis extract with serial plasma sampling

exposure

Controlled oral THC and oromucosal extract dosing

limitations

A controlled human pharmacokinetic study with the metabolites measured. Oral and oromucosal routes only; it does not describe smoked exposure.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Human

plain_language

The drug is measured alongside the two metabolites it becomes.

primary_references

[thc-p21078841] Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. (2011). https://pubmed.ncbi.nlm.nih.gov/21078841/ DOI: 10.1373/clinchem.2010.152439

tissue_or_cell_type

Plasma

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 517–528

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled oral THC and oromucosal cannabis extract with serial plasma sampling · source_derived_draft · unverified_draft

### thc-thc-metabolites Plasma cannabinoid pharmacokinetics following controlled oral THC and oromucosal cannabis extract administration resolved the time courses of THC and its metabolites. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The drug is measured alongside the two metabolites it becomes. organism: Human tissue_or_cell_type: Plasma experimental_model: Controlled oral THC and oromucosal cannabis extract with serial plasma sampling limitations: A controlled human pharmacokinetic study with the metabolites measured. Oral and oromucosal routes only; it does not describe smoked exposure. exposure: Controlled oral THC and oromucosal extract dosing evidence_span: {"source_cache": "artifacts/thc-research/21078841.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9", "start_char": 0, "end_char": 1727, "text_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9"} [thc-p21078841] Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. (2011). https://pubmed.ncbi.nlm.nih.gov/21078841/ DOI: 10.1373/clinchem.2010.152439

evidence_span

{"source_cache": "artifacts/thc-research/8856831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0", "start_char": 0, "end_char": 1652, "text_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0"}

experimental_model

Spatial memory testing in rats with a CB1 antagonist

exposure

THC with antagonist pretreatment

limitations

The antagonist arm is what makes this a receptor mechanism rather than a general sedative effect.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rat

plain_language

The memory effect runs through the receptor, not through general sedation.

primary_references

[thc-p8856831] Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism. (1996). https://pubmed.ncbi.nlm.nih.gov/8856831/ DOI: 10.1007/bf02246347

tissue_or_cell_type

Hippocampus and behaviour

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 439–450

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Spatial memory testing in rats with a CB1 antagonist · source_derived_draft · unverified_draft

### thc-thc-spatial-memory THC impaired spatial memory through a cannabinoid receptor mechanism, since the impairment was prevented by receptor blockade. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The memory effect runs through the receptor, not through general sedation. organism: Rat tissue_or_cell_type: Hippocampus and behaviour experimental_model: Spatial memory testing in rats with a CB1 antagonist limitations: The antagonist arm is what makes this a receptor mechanism rather than a general sedative effect. exposure: THC with antagonist pretreatment evidence_span: {"source_cache": "artifacts/thc-research/8856831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0", "start_char": 0, "end_char": 1652, "text_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0"} [thc-p8856831] Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism. (1996). https://pubmed.ncbi.nlm.nih.gov/8856831/ DOI: 10.1007/bf02246347

evidence_span

{"source_cache": "artifacts/thc-research/8679694.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4", "start_char": 0, "end_char": 967, "text_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4"}

experimental_model

Cloning, expression and functional characterisation of the murine CB2 receptor

exposure

Heterologous expression with ligand binding

limitations

Establishes a second, peripheral receptor. It is the mouse orthologue.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Mouse receptor

plain_language

A second receptor exists, and it sits mostly outside the brain.

primary_references

[thc-p8679694] Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. (1996). https://pubmed.ncbi.nlm.nih.gov/8679694/ DOI: 10.1016/0167-4781(96)00047-4

tissue_or_cell_type

Peripheral and immune tissue

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 88–99

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning, expression and functional characterisation of the murine CB2 receptor · source_derived_draft · unverified_draft

### thc-cb2-cloned The murine CB2 peripheral cannabinoid receptor was cloned, expressed and shown to function as a cannabinoid receptor distinct from the brain receptor. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: A second receptor exists, and it sits mostly outside the brain. organism: Mouse receptor tissue_or_cell_type: Peripheral and immune tissue experimental_model: Cloning, expression and functional characterisation of the murine CB2 receptor limitations: Establishes a second, peripheral receptor. It is the mouse orthologue. exposure: Heterologous expression with ligand binding evidence_span: {"source_cache": "artifacts/thc-research/8679694.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4", "start_char": 0, "end_char": 967, "text_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4"} [thc-p8679694] Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. (1996). https://pubmed.ncbi.nlm.nih.gov/8679694/ DOI: 10.1016/0167-4781(96)00047-4

evidence_span

{"source_cache": "artifacts/thc-research/30639103.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f", "start_char": 0, "end_char": 1108, "text_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f"}

experimental_model

X-ray crystallography of the human CB2 receptor

exposure

Ligand-bound receptor crystallography

limitations

A companion structure for the second receptor, from the same structural programme.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Human receptor

plain_language

The two receptors are shaped differently, which is why drugs can prefer one.

primary_references

[thc-p30639103] Crystal Structure of the Human Cannabinoid Receptor CB2. (2019). https://pubmed.ncbi.nlm.nih.gov/30639103/ DOI: 10.1016/j.cell.2018.12.011

tissue_or_cell_type

Purified receptor

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 127–138

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of the human CB2 receptor · source_derived_draft · unverified_draft

### thc-cb2-structure The crystal structure of the human CB2 receptor was determined, showing how its binding pocket differs from that of CB1. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The two receptors are shaped differently, which is why drugs can prefer one. organism: Human receptor tissue_or_cell_type: Purified receptor experimental_model: X-ray crystallography of the human CB2 receptor limitations: A companion structure for the second receptor, from the same structural programme. exposure: Ligand-bound receptor crystallography evidence_span: {"source_cache": "artifacts/thc-research/30639103.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f", "start_char": 0, "end_char": 1108, "text_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f"} [thc-p30639103] Crystal Structure of the Human Cannabinoid Receptor CB2. (2019). https://pubmed.ncbi.nlm.nih.gov/30639103/ DOI: 10.1016/j.cell.2018.12.011

evidence_span

{"source_cache": "artifacts/thc-research/38583809.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1", "start_char": 0, "end_char": 1645, "text_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1"}

experimental_model

Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein

exposure

THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1

limitations

Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Human enzymes

plain_language

Three enzymes share the job, and a fat-carrying protein changes how fast they do it.

primary_references

[thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191

tissue_or_cell_type

Recombinant system

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 543–554

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein · source_derived_draft · unverified_draft

### thc-multiple-cyps CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Three enzymes share the job, and a fat-carrying protein changes how fast they do it. organism: Human enzymes tissue_or_cell_type: Recombinant system experimental_model: Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein limitations: Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system. exposure: THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1 evidence_span: {"source_cache": "artifacts/thc-research/38583809.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1", "start_char": 0, "end_char": 1645, "text_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1"} [thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

THC and methanandamide compared in CB1 knockout and wild-type mice

exposure

THC and a stable anandamide analogue across genotypes

limitations

The comparison of two agonists across the same genotypes is what shows the receptor accounts for the drug but not for everything cannabinoid-like.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Mouse

plain_language

Take the receptor away and the drug stops working, though not every cannabinoid-like effect disappears with it.

primary_references

[thc-p14718593] Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1 knockout and wild-type mice. (2004). https://pubmed.ncbi.nlm.nih.gov/14718593/ DOI: 10.1124/jpet.103.055376

tissue_or_cell_type

Whole body

trigger_kind

machinery_impairment Imported condition classification; unverified.

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 426–437

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · THC and methanandamide compared in CB1 knockout and wild-type mice · source_derived_draft · unverified_draft

### thc-thc-requires-cb1 THC and methanandamide had differential effects in CB1 knockout and wild-type mice, with the effects of THC dependent on the receptor while some effects of the anandamide analogue were not. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Take the receptor away and the drug stops working, though not every cannabinoid-like effect disappears with it. organism: Mouse tissue_or_cell_type: Whole body experimental_model: THC and methanandamide compared in CB1 knockout and wild-type mice limitations: The comparison of two agonists across the same genotypes is what shows the receptor accounts for the drug but not for everything cannabinoid-like. exposure: THC and a stable anandamide analogue across genotypes evidence_span: {"source_cache": "artifacts/thc-research/14718593.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "422efbafe3e999138f4591acf2a7e5126919ba85d84637aeb320927062c5b2a8", "start_char": 0, "end_char": 1836, "text_sha256": "422efbafe3e999138f4591acf2a7e5126919ba85d84637aeb320927062c5b2a8"} [thc-p14718593] Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1 knockout and wild-type mice. (2004). https://pubmed.ncbi.nlm.nih.gov/14718593/ DOI: 10.1124/jpet.103.055376

evidence_span

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experimental_model

Quantified potency and intrinsic activity of cannabinoid ligands on cAMP in CHO cells expressing human CB1

exposure

A ligand series measured for both stimulation and inhibition of cAMP, with and without forskolin

limitations

Reports that the receptor couples to Gs as well as Gi and that ligands differ between the two pathways. It is a transfected overexpression system, where Gs coupling is more readily observed.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Human receptor in CHO cells

plain_language

The same receptor can push cAMP up as well as down, and which way depends on which drug is bound.

primary_references

[thc-p9864268] Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses. (1998). https://pubmed.ncbi.nlm.nih.gov/9864268/ DOI: 10.1016/s0022-3565(24)37876-0

tissue_or_cell_type

Transfected cells

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 179–190

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantified potency and intrinsic activity of cannabinoid ligands on cAMP in CHO cells expressing human CB1 · source_derived_draft · unverified_draft

### thc-agonist-specific-trafficking Cannabinoid receptors coupled to both Gs and Gi and could consequently stimulate or inhibit cAMP formation, with an identical rank order of agonist potency in both assays but markedly different intrinsic activities, anandamide and CP-55,940 being much less efficacious at stimulating cAMP than at inhibiting it, and forskolin enhancing the potency of some agonists a hundred-fold while not affecting others. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The same receptor can push cAMP up as well as down, and which way depends on which drug is bound. organism: Human receptor in CHO cells tissue_or_cell_type: Transfected cells experimental_model: Quantified potency and intrinsic activity of cannabinoid ligands on cAMP in CHO cells expressing human CB1 limitations: Reports that the receptor couples to Gs as well as Gi and that ligands differ between the two pathways. It is a transfected overexpression system, where Gs coupling is more readily observed. exposure: A ligand series measured for both stimulation and inhibition of cAMP, with and without forskolin evidence_span: {"source_cache": "artifacts/thc-research/9864268.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a39487ffec2ec3efa585fd49076c7498e8db3bf0ab943fe267e431b93dc7483d", "start_char": 0, "end_char": 1502, "text_sha256": "a39487ffec2ec3efa585fd49076c7498e8db3bf0ab943fe267e431b93dc7483d"} [thc-p9864268] Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses. (1998). https://pubmed.ncbi.nlm.nih.gov/9864268/ DOI: 10.1016/s0022-3565(24)37876-0

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/thc-research/9862397.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f", "start_char": 0, "end_char": 1576, "text_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f"}

experimental_model

Memory impairment by THC or anandamide with SR141716A pretreatment

exposure

THC or anandamide with a CB1 antagonist

limitations

Shows the antagonist rescues the impairment for both the drug and the natural ligand.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rat

plain_language

Blocking the receptor protects the memory, whichever agonist caused the problem.

primary_references

[thc-p9862397] The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide. (1998). https://pubmed.ncbi.nlm.nih.gov/9862397/ DOI: 10.1007/s002130050733

tissue_or_cell_type

Behaviour

trigger_kind

machinery_impairment Imported condition classification; unverified.

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 452–463

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Memory impairment by THC or anandamide with SR141716A pretreatment · source_derived_draft · unverified_draft

### thc-antagonist-rescues-memory The CB1 antagonist SR141716A attenuated the memory impairment produced by THC or by anandamide. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Blocking the receptor protects the memory, whichever agonist caused the problem. organism: Rat tissue_or_cell_type: Behaviour experimental_model: Memory impairment by THC or anandamide with SR141716A pretreatment limitations: Shows the antagonist rescues the impairment for both the drug and the natural ligand. exposure: THC or anandamide with a CB1 antagonist evidence_span: {"source_cache": "artifacts/thc-research/9862397.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f", "start_char": 0, "end_char": 1576, "text_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f"} [thc-p9862397] The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide. (1998). https://pubmed.ncbi.nlm.nih.gov/9862397/ DOI: 10.1007/s002130050733

evidence_span

{"source_cache": "artifacts/thc-research/2165569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db", "start_char": 0, "end_char": 1256, "text_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db"}

experimental_model

Cloning and heterologous expression of a complementary DNA from rat brain

exposure

Cannabinoid binding and adenylate cyclase inhibition in the transfected cells

limitations

The founding cloning paper. It establishes a receptor, which is what displaced the membrane-disruption explanation of cannabinoid action.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rat receptor expressed in cells

plain_language

Cannabis acts on a specific receptor, not by melting cell membranes as was assumed.

primary_references

[thc-p2165569] Structure of a cannabinoid receptor and functional expression of the cloned cDNA. (1990). https://pubmed.ncbi.nlm.nih.gov/2165569/ DOI: 10.1038/346561a0

tissue_or_cell_type

Brain and neural cell lines

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 62–73

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and heterologous expression of a complementary DNA from rat brain · source_derived_draft · unverified_draft

### thc-cb1-cloned A cloned complementary DNA encoded a G protein-coupled receptor that inhibits adenylate cyclase in a dose-dependent, stereoselective and pertussis-toxin-sensitive manner, is more responsive to psychoactive than to non-psychoactive cannabinoids, and whose messenger RNA is found in the brain regions that have cannabinoid receptors. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Cannabis acts on a specific receptor, not by melting cell membranes as was assumed. organism: Rat receptor expressed in cells tissue_or_cell_type: Brain and neural cell lines experimental_model: Cloning and heterologous expression of a complementary DNA from rat brain limitations: The founding cloning paper. It establishes a receptor, which is what displaced the membrane-disruption explanation of cannabinoid action. exposure: Cannabinoid binding and adenylate cyclase inhibition in the transfected cells evidence_span: {"source_cache": "artifacts/thc-research/2165569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db", "start_char": 0, "end_char": 1256, "text_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db"} [thc-p2165569] Structure of a cannabinoid receptor and functional expression of the cloned cDNA. (1990). https://pubmed.ncbi.nlm.nih.gov/2165569/ DOI: 10.1038/346561a0

evidence_span

{"source_cache": "artifacts/thc-research/19322169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443", "start_char": 0, "end_char": 1794, "text_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443"}

experimental_model

Region-specific CB1 manipulation with memory testing

exposure

THC with hippocampal CB1 manipulation

limitations

Localises the effect to one structure, which the whole-animal antagonist studies cannot do.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rodent

plain_language

It is the receptors in one brain structure that account for the memory effect.

primary_references

[thc-p19322169] Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. (2009). https://pubmed.ncbi.nlm.nih.gov/19322169/ DOI: 10.1038/npp.2009.31

tissue_or_cell_type

Hippocampus

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 465–476

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Region-specific CB1 manipulation with memory testing · source_derived_draft · unverified_draft

### thc-hippocampal-cb1-memory Hippocampal CB1 receptors mediate the memory-impairing effects of THC. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: It is the receptors in one brain structure that account for the memory effect. organism: Rodent tissue_or_cell_type: Hippocampus experimental_model: Region-specific CB1 manipulation with memory testing limitations: Localises the effect to one structure, which the whole-animal antagonist studies cannot do. exposure: THC with hippocampal CB1 manipulation evidence_span: {"source_cache": "artifacts/thc-research/19322169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443", "start_char": 0, "end_char": 1794, "text_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443"} [thc-p19322169] Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. (2009). https://pubmed.ncbi.nlm.nih.gov/19322169/ DOI: 10.1038/npp.2009.31